Ebola: Mali Reports New Cases

New transmission chain alarms health authorities.

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The West African nation of Mali is reporting a second confirmed case of Ebola as well as two new probable cases, all of them fatal.

Note that the WHO said the situation in the three hardest-hit countries remains grim, although there is some evidence that, on a nationwide basis, the case numbers are stabilizing in Liberia and Guinea.

The West African nation of Mali is reporting a second confirmed case of Ebola as well as two new probable cases, all of them fatal.

But all the cases are related -- through separate chains of transmission -- to the outbreak in neighboring Guinea, which shares a 480-mile border with Mali.

The report comes as the WHO says the worldwide toll of the Ebola epidemic has reached 14,098 cases, with 5,160 deaths. The vast majority of those -- 14,068 cases and 5,147 deaths -- are in Guinea, Liberia, and Sierra Leone.

With the release of Craig Spencer, MD, from New York City's Bellevue Hospital, the U.S. currently has no cases of the disease, although four have been diagnosed on American soil. All but one -- Liberian native Thomas Eric Duncan -- have recovered.

In Mali, health officials continue to monitor 67 contacts of Fanta Condé, the child who was the country's first case, but 41 have passed through the 21-day surveillance period without symptoms.

But officials are alarmed by the new cases, where the investigation is just beginning.

So far, 28 healthcare workers who cared for the second confirmed case -- a nurse at the private Pasteur Clinic in the capital city of Bamako -- have been identified and placed under observation.

Investigators said the chain of events leading to the death began in the Siguiri prefecture of Guinea Oct. 17 when a 70-year-old man developed symptoms and was admitted to a private clinic there the following day.

When he did not improve, he was transferred to another clinic, this one across the border in Mali, and then traveled by car with four family members to the Pasteur Clinic in Bamako.

He was suffering from acute kidney failure, a common complication in the late stages of Ebola, and died Oct. 27. A friend who visited him died abruptly, according to officials, and because no samples are available for testing both are considered probable cases of Ebola.

The nurse, one of those who cared for the man, died Oct. 11, and testing confirmed Ebola.

The body of the man was taken to a mosque in Bamako for a ritual washing ceremony and then back to his native village of Kouremale in Guinea for funeral and burial.

The WHO said investigators assume there were many mourners. Funeral and burial customs have been associated with spread of Ebola, and one of the measures being taken against the epidemic is a program of safe burials.

Meanwhile, the man's first wife died Oct. 6 and his daughter died Nov. 10, both of an undiagnosed disease. His brother and second wife are under care at an Ebola treatment center in Gueckedou, Guinea, and the man's son has tested positive for Ebola.

All except the daughter were with the patient during the car trip to Bamako.

Taken together, the evidence strongly suggests the man's cause of death was the virus, the WHO said in a report.

Intense Transmission

Meanwhile the WHO said the situation in the three hardest-hit countries remains grim, although there is some evidence that, on a nationwide basis, the case numbers are stabilizing in Liberia and Guinea.

But the agency cautioned that several regions in each country continue to have intense transmission.

In Guinea, for instance, the capital of Conakry and the southern region of Macenta between them reported 40 new cases in the past week, although the region of Gueckedou, where the outbreak began, has one reported one case in the past 2 weeks.

And in Sierra Leone, there is no evidence of a letup, the WHO said. The country had 421 new cases last week (compared with 135 in Guinea and 97 in Liberia).

In a snapshot of the regional and global response, the agency said that:

24% of the planned 4,611 beds in Ebola treatment units are up and running. They represent 19 of 53 planned units.

38% of the planned 370 safe burial teams are working.

All districts in each country now have access within 24 hours to Ebola testing.

49% of the $260 million that the agency estimates it will need has been received and another 15% has been pledged, leaving a gap of 36%.

Clinical Trials Planned

Elsewhere, the international medical aid organization Medecins San Frontieres (MSF) or Doctors Without Borders said it will host three clinical trials in the region in order to try to find an Ebola therapy.

Also, the University of Oxford in England will test the antiviral drug brincidofovir at MSF's ELWA3 Ebola treatment center in Monrovia, while the French National Institute of Health and Medical Research will test the antiviral favipiravir in Gueckedou. The Antwerp Institute of Tropical Medicine will test the efficacy of convalescent whole blood and plasma therapy in Conakry.

All three approaches have been used on an empirical basis -- several U.S. patients, for instance, got blood products from Ebola survivors -- but it has been difficult to know whether they had any effect, either positive or negative.

"These three trials are part of the first phase of research aimed at finding the best treatment to cure patients with Ebola," said Denis Malvy, MD, PhD, of the Universite Victor Segalen in Bordeaux, France, who will lead the French trial in Guinea.

He said in a statement that the three trial boards will work closely together "so that any new fact can be discussed rapidly and our research plans can be adapted accordingly."

"We need to keep in mind that there is no guarantee that these therapies will be the miracle cure," said MSF's Annick Antierens, MD. "But we need to do all we can to try the products available today to increase the chances of finding an effective treatment against Ebola."

The investigators, led by G. Marshall Lyon, MD, of Emory University Hospital in Atlanta, report how they treated patient 1 and patient 2 -- Kent Brantly, MD, and Nancy Writepol -- who contracted the disease while involved in Ebola care in Liberia, but survived after they were airlifted to Emory.

Brantly, in fact, is a co-author on the report, which paints a day-by-day picture of the clinical course of the disease and how clinicians struggled to overcome the virus.

A key factor was coping with "substantial intravascular volume depletion and marked electrolyte abnormalities," the authors write. The patients typically were given between 3 and 5 L of intravenous fluids daily in addition to what they were able to drink.

Both patients had hypovolemia, hypokalemia, hypocalcemia, and hypoalbuminemia, while Brantly also had hyponatremia. They also both had thrombocytopenia but without evidence of coagulation disorders.

One consequence of the hypovolemia was edema, to the extent that during her flight to Atlanta, workers could not get a blood sample from Writepol owing to anasarca.

Both Brantly and Writepol famously were given the investigational antibody cocktail Zmapp, but there's no way to judge its effect, the authors note. Both patients had subjective and objective improvements after taking the medication, but that concomitant care might also have produced the effect, Lyon and colleagues note.

The investigators argued that the key factors in the recovery of Brantly and Writepol appeared to be "aggressive volume and electrolyte replacement with a special focus on replacing potassium and calcium."

With "only the modest support that is available in treatment centers in West Africa," about three patients in 10 are surviving Ebola, they note in an accompanying editorial.

And, absent modern care, "it is unlikely that the patient treated in Germany would have survived."

"Although this news is encouraging for patients with access to an intensive care unit, it is only more discouraging for those in areas where such infections are endemic and even basic care is often unavailable," Baden and Rubin wrote.

Lyon and co-authors disclosed no relevant relationships with industry.

Rubin and Baden disclosed no relevant relationships with industry.

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner